7. PROJECT SUMMARY/ABSTRACT Since 1980, the global prevalence of overweight and obesity increased by 27.5% in adults and by 47.1% in children. Although rates appear to have tapered off over recent years in many developed countries, steady increases continue to be reported in developing countries, most particularly in Africa. Between 1990 and 2010, the number of overweight and obese children doubled in Africa and in 2017, the highest prevalence of overweight and obesity among young children was found in the Southern Africa U.N region. In South Africa?s Vhembe district, the prevalence of childhood overweight and obesity increased by a factor of 2.7 between 2008 and 2015, reaching 40%. Concomitantly, earlier onset of puberty has been observed globally and it has been suggested that increasing trends in obesity prevalence may play a role. Although changes in diet and physical activity likely influence these trends, growing evidence suggests that exposure to chemicals that disrupt endocrine function may be a factor. A total of 88 countries practice Indoor Residual Spraying (IRS), the use insecticides on the interior walls of residences to control malaria, resulting in high exposure to endocrine-disrupting chemicals such as dichlorodiphenyl trichloroethane (DDT) and pyrethroids. DDT, a known environmental estrogen, increases body fat and advances puberty in female rodents while DDT?s breakdown product dichlorodiphenyl dichloroethylene (DDE), an antiandrogen, delays puberty in males. Few human studies have investigated associations between DDT exposure and body composition or pubertal onset but studies of DDE found relations with delayed puberty in boys and our preliminary studies suggest that DDE is obesogenic in South African girls. Animal studies show that pyrethroids, which are androgenic, delay puberty onset in females and accelerate puberty in males but this question has only been studied by one group in China. To our knowledge, no study has investigated the impact of exposure to DDT or pyrethroids on body composition, pubertal onset or endocrine function in peripubertal African children. We propose to address these important knowledge gaps by extending a unique birth cohort study of rural South African children with extensive data on health, exposure and confounders, rich research infrastructure and strong community networks. We aim to identify the levels and determinants of exposure to DDT/E and pyrethroids among children aged 7 to 10 and determine whether pre- and postnatal exposure to these insecticides is associated with: 1) altered body composition, 2) puberty timing and tempo, and 3) hormone levels. This study will provide policy-makers with data to better understand the determinants of the dramatic rise in obesity and the acceleration of puberty in South Africa and other developing countries. It will also provide essential information on the potential unintended consequences of IRS to malaria-endemic countries and international bodies so that they can determine the safest and most sustainable methods to control malaria.